Somehow it works time to time now.
Besides the SMTP-Server Timeout I also could not update incoming E-Mails with Thunderbird btw.
I did change nothing. The where two Windows 10 updated since first post. Also as you heard I am using NordVPN.
Avast Settings arent default, since my second post:
Protection - Core Shields - E-Mail
yes Enable Email Shield
yes Scan Inbound
yes Scan Outbound
yes Add Signature
no Mark Subjekt
no Scan Attachment MS Outlook - I dont use Outlook
yes Generate Report
I also never expierenced this kind of Issue. I use Avast since 2010 or so.